Hydroxyapatite (HA), Ca10(PO4)6(OH)2, is the main mineral component of bone tissue. Given its high biocompatibility and natural affinity for biological substances, hydroxyapatite is commonly used in bone and osteocartilage substitution/regeneration applications and as a carrier for proteins, genes, stem cells, growth factors, active substances, etc.
It is well known that hydroxyapatite has a hexagonal crystal lattice comprising phosphate ions, hydroxyl ions and calcium ions, the latter with hexavalent or tetravalent coordination (positions 6h and 4f).
It is also well known that the structure of hydroxyapatite is capable of accommodating various types of ionic substitutions at the sites of the phosphate ion, hydroxyl ion and calcium ion, without any collapse occurring in the structure.
In other words, hydroxyapatite is a material that can be doped with different types of ions without causing a phase degradation thereof.
In addition to the doping of hydroxyapatite carried out with the aim of enhancing its biomimetic properties in relation to the mineral phase constituting bone tissue, numerous substitutions have been made with ions capable of imparting magnetic properties, such as Fe, Co, Mn and La.
In particular, Mayer et al. (Journal of Inorganic Biochemistry 1992, 45, 129-133) reported the synthesis of hydroxyapatite doped with ferric ions (Fe3+HA) using Fe(NO3)3 as reagent. According to the authors, the ferric ions were not incorporated into the apatite lattice but were present in the apatite itself in the form of Fe-00H.
Wu et al. (Nanotechnology 2007, 18, 165601-10) reported the synthesis of hydroxyapatite doped with ferrous ions (Fe2+HA) using FeCl2*4H2O as Fe2+ ion source. However, they obtained a product with magnetic properties only in the case in which hydroxyapatite was accompanied by the formation of secondary magnetic phases, such as magnetite.
Ming Jang et al. (Review, Condensed Matter and Materials Physics, 2002, 66, 224107-224115) doped hydroxyapatite with Fe2+ and Fe3+ ions, starting from Ca(NO3)2 and Fe(NO3)2 solutions added drop by drop to an ammonium phosphate solution. The article does not provide any indication as to a possible intrinsic magnetization of the hydroxyapatite.
One of the most relevant limitations connected with the use of scaffolds for bone or osteocartilage regeneration regards the difficulty of controlling the development and speed of the processes of cellular differentiation and angiogenesis at the scaffold implantation site.
These processes are favoured by the speed of migration of bone tissue growth factors and vascularization factors to the implantation site.
Control over the migration of specific factors to the implantation site, according to patient needs and for a prolonged period, is of enormous importance for favouring osseointegration of the prosthesis and the regeneration of the bone tissue, and hence for the healing of the patient.
In this sector, therefore, there is a strongly felt need for a carrier and release system for biological substances and drugs which can enable control of the migration of growth factors, vascularization factors or other biological substances capable of favouring and accelerating osseointegration and bone regeneration. A need is also felt for a drug carrier system which can be guided in a precise and accurate manner so as to release the drug directly, in a selective manner, and according to the real quali-quantitative requirements, only at the site affected by the pathology.
In the sector there also exists a need for a prosthesis for bone and osteocartilage regeneration which is biocompatible at the same time and can be manipulated and constrained in the specific implantation position in vivo by means of a control system outside the patient's body, thus eliminating the present necessity of invasive fixing systems.